Elimination of Listeria monocytogenes requires the recognition of L monocytogenes antigens by T cells. T[unreadable] cell activation is initiated by the binding of the T cell receptor (TCP) on the T cell surface to cognate pMHC[unreadable] ligands on antigen presenting cells (APCs). While most work on T cell activation has focused on the[unreadable] interaction of the TCR with the antigenic peptide bound to MHC, recent work demonstrates that nonantigenic,[unreadable] endogenous self peptides play important roles in cooperating with antigenic peptides to allow for[unreadable] sufficient signaling to activate T cells. This suggests that variability of endogenous peptides could play a[unreadable] critical role in determining the outcome of an infection. In addition, the role of endogenous peptides suggests[unreadable] new ways to think about peptide antagonism, a phenomenon that is still unexplained. Here we propose to[unreadable] use mathematical modeling with genetic and biochemical experiments to lend new insights into how[unreadable] endogenous peptides contribute to the initial signaling events that trigger T cell activation. We propose to[unreadable] examine the role of endogenous pMHC ligands in mediating signaling during the recognition of L.[unreadable] monocytogenes. We also propose to determine the interplay between TCR signaling stimulated by[unreadable] endogenous, agonist, and antagonist ligands with a view toward determining the mechanism underlying[unreadable] antagonism in vitro. Lastly, we hope to for the first time try and establish a model for studying antigenic[unreadable] antagonism in vivo. We believe that these studies will lead to a better understanding of how the immune[unreadable] system sense and eliminates pathogens.